The proposed research will examine the impact of homozygous sickle cell disease (HbSS) on protein, glucose, and lipid metabolism and the contribution of these substrates to energy expenditure under basal conditions and during nutrient availability. In addition, the potential of an increased protein intake to improve these variables will be determined. Whole-body and skeletal muscle protein synthesis and breakdown, endogenous glucose production, whole-body and forearm glucose utilization, whole-body lipolysis, and energy expenditure will be measured in the basal state and during an intravenous nutrient infusion approximating the composition of a normal diet in control and HbSS subjects. Furthermore, on two additional occasions, a subset of the HbSS subjects will receive an intravenous nutrient infusion providing increased protein intake with or without an increase in energy intake to determine the most suitable means for meeting the potentially increased protein needs of HbSS patients. To date, 3 studies have been completed and the preliminary data suggest that resting energy expenditure as well as basal whole-body protein breakdown and synthesis, glucose utilization, endogenous glucose production, and carbohydrate and protein oxidation are elevated while basal whole-body lipolysis and lipid oxidation are decreased with HbSS. Furthermore, data from the nutrient infusion studies suggest that the most viable means of meeting the additional protein demands created by HbSS is via an increase in protein intake without an increase in energy intake. Findings from this research will provide valuable information for developing optimal nutritional regimens for HbSS patients with the goal of improving their nutritional well-being and will provide the basis for submitting applications for gaining research support for future studies through conventional granting mechanisms.